With the rat as the experimental animal, the aims of this research are to test the following assumptions: a) treatments which markedly alter anterior pituitary function and structure, such as dietary restriction of calories and of the essential amino acid tryptophan, (precursor of serotonin), as well as chronic ingestion of d,1-parachlorophenylalanine (PCPA - an enzyme inhibitor able to mimic the growth retarding effects of nutritional restriction) initiated in early life, result in slower growth, delayed development and longer lifespan as compared to controls; b) the effects of these dietary and pharmacologic manipulations can be enhanced by simultaneous administration of gonadal, adrenal and thyroid hormones; c) rats subjected to the above treatments are physiologically younger (in terms of adaptive and reproductive functions) and show a reduced incidence of age-related pathology than control rats of the same chronologic age; and d) the treatments proposed may influence growth, development and aging either by interfering with protein synthesis generally and/or synthesis of hypothalamic and pituitary hormones, or by selectively altering the production of monoamines. After determining optimal methodology in terms of the appropriate critical age at which these treatments should be initiated and the maximal effectiveness of treatment in terms of dose and duration, we will assess endocrinologic, histologic and neurochemical differences between controls and experimental rats. We will compare the effects of the proposed treatments on sexual and reproductive competence, adaptive capability, neurotransmission and lifespan to advance our hypothesis that growth, development and aging are regulated by biological clocks acting through CNS-endocrine mechanisms. From this basic knowledge of some of the causal and mechanistic aspects of development and aging, the possibility of modifying the aging process, nutritionally and/or neuropharmacologically in the laboratory and ultimately the clinic, becomes a realizable goal.